Antigen-Driven Evolution of B Lymphocytes in Coronary Atherosclerotic Plaques

Abstract

Recent data indicated that adaptive immunity is involved in the process of atherogenesis. Oligoclonal recruitment of T lymphocytes has been described in coronary plaques of patients with acute coronary syndrome. However, the nature of immune response remains to be determined. In the present study, we examined the Ab response in six coronary plaques obtained by endoluminal directional atherectomy. The IgG1/κ-coding gene repertoires of B lymphocytes present in circulating blood and in coronary plaques were cloned and analyzed. In all of the six plaques, we observed 1) a skewed usage of heavy and light IgG1/κ Ab-coding genes, 2) an oligoclonal distribution of VK, JK, and VH, DH, and JH genes with overrepresentation of some rarely used IgG genes, and 3) the unequivocal signs of Ag-driven clonal expansion and evolution of B cells. The data document for the first time the presence of a local Ag-driven clonal evolution of B cells in human atherosclerotic plaques.

Lymphocytes and the Adventitial Immune Response in Atherosclerosis

“…B lymphocyte aggregates have been observed within the nodular centers of adventitial ATLOs and may undergo selection, maturation, and antibody production following antigen presentation by dendritic cells 7,10 . Real-time PCR performed on directional artherectomy samples obtained from coronary arteries of six patients with coronary artery disease demonstrated evidence of antigen-driven clonal expansion and evolution of B lymphocytes in human atherosclerotic plaques 39 . Additionally, in their survey of inflammatory cell infiltration in atherosclerosis, Parums and Mitchinson noted that advanced plaques with evidence of medial attenuation showed significant adventitial plasma cell and B lymphocyte accumulation 19,40 .…”

Cardiotoxicity of Anticancer Drugs: The Need for Cardio-Oncology and Cardio-Oncological Prevention

“…It is clear that the diagnostic and prognostic value of other biomarkers used to monitor cardiovascular damage, such as myeloperoxidase (72), should also be validated for clinical use in cardio-oncology. Genomics, proteomics, and/or recently identified oligoclonal B-cell repertoires (77) may provide us with genomic profiles and serological biomarkers for assessment of cardiotoxicity in the foreseeable future.…”

Ancestral resurrection of anthropoid estrogen receptor β demonstrates functional consequences of positive selection

“…Detecting adaptively evolving genes is a powerful way in which evolutionary advantages and candidate genes for disease can be identified (Burioni et al, 2009; Carrigan et al, 2015; Crespi et al, 2007; Hanson and Gluckman, 2008; Hou et al, 2009); however, it has become apparent that experimental evidence for adaptation is necessary to confirm the functional importance of inferred evolutionary changes (Nozawa et al, 2009). To determine the functional consequences of amino acid replacements in estrogen receptors we used ancestral gene resurrection (Bridgham et al, 2006; Thornton, 2001).…”